Objective
To investigate the features of clinic and genetic of Chinese children with very early onset inflammatory bowel disease (VEO-IBD) .
Methods
A total of 30 Chinese children diagnosed with VEO-IBD definitely were enrolled in the study. The onset age, clinical manifestation, body development, blood test and drug efficacy were investigated. Next generation sequencing (NGS) based on target gene sequencing panel and Sanger sequencing were used to analyze the 50 candidate genes reported.
Results
Among the 30 VEO-IBD children, the meaningful gene mutations were found in 15 cases, of whom 13 had mutations in IL-10RA gene, 1 had hemizygote mutation in CYBB gene and 1 had compound heterozygote mutation in SLC37A4 gene. A total of 8 mutation sites of IL-10RA were found, of which p.R101W was found in 10 cases, p.K173NfsX7 in 5 cases, p.R165X (414) in 2 cases, p.R117H in 2 cases, p.P146fs in 1 case, p.G141R in 1 case, p.V100G in 1 case and p.Y64C in 1 case. As compared to other 15 patients without mutation or without meaningful mutation, those with meaningful mutations had earlier onset age[0.5 (0.03, 2) months vs 4 (0.23, 9) months, P<0.05], higher proportion of cases with onset age less than 1 month old (66.7% vs. 26.7%, P<0.05) , higher proportion of cases with perianal lesions (73.3% vs. 36.4%, P<0.05) and lower remission rate after drug therapy (0 vs 46.7%, P<0.01) .
Conclusions
The frequency of monogenic mutation in Chinese VEO-IBD pediatric patients is quite high, and the most common mutation is IL-10RA gene mutation. VEO-IBD patients with gene mutation have earlier onset age, higher incidence of perianal lesion and lower remission rate after drug therapy.
Key words:
Pediatric inflammatory bowel disease; Very early onset inflammatory bowel disease; Interleukin 10 receptor; Primary immunodeficiency disease; Inherited metabolic diseases